From bench to bedside - is there a role of IL-17 drugs in rheumatoid arthritis?

INTRODUCTION: IL-17 has been described as a pro-inflammatory cytokine that is relevant in the seronegative spondylarthritides with IL-17 targeted therapies being licensed for their treatment.There is evidence to demonstrate that IL-17 is found in RA joints and contributes to the pro-inflammatory cascade. This results in synovial hyperplasia and osteoclastogenesis thus causing joint destruction and bony erosions. AREAS COVERED: This review article summarizes trials that have studied the use of IL-17 targeted therapies in RA patients who have failed conventional synthetic disease-modifying therapy (C-DMARDS) and biologic DMARDS. EXPERT OPINION: The trials that have studied IL-17 inhibitors in RA patients have only shown a modest improvement in disease activity. In several trials, the primary endpoint was not achieved whilst in others, when comparing with existing licensed biologics for RA, did not demonstrate any superiority.Tissue Necrosis Factor-alpha (TNF-α) likely plays more of a pivotal role in the pathogenesis of RA with IL-17 having a synergistic effect. Therefore, in our opinion, IL-17 inhibitors as an independent therapy for RA are less likely to provide a cost-effective benefit. There may be scope to potentially combine it with TNF-α-inhibitors (TNF-i), but this requires further research especially with the potential concerns related to increased immunosuppression.

Social determinants of low uptake of childhood vaccination in high-risk squatter settlements in Karachi, Pakistan - A step towards addressing vaccine inequity in urban slums.

Background: Routine vaccination has remained historically low in major urban pockets of Pakistan, and now lags behind rural vaccination rates. Grossly insufficient publicly funded primary healthcare infrastructure, heterogeneous mix of providers and multi-ethnicity of populations pose challenges in the delivery of essential health services. This paper ascertains factors associated with uptake of routine childhood vaccination, using Pentavalent-3 vaccine, as a proxy indicator for completion of age-appropriate vaccines in urban slums of Karachi, at high risk of Polio and vaccine preventable disease outbreaks. Methods: Data was drawn from baseline assessment of an urban immunization delivery pilot project in urban slums of Karachi, Pakistan. The study sample comprised of 2,097 households with children aged 4-12 months, sampled through a cross-sectional cluster survey, applying a structured questionnaire. Multivariable logistic regression was used to determine the association between Penta-3 vaccination, as the outcome variable, and predictor variables including socio-demographic characteristics and healthcare access factors. Results: The findings showed that the likelihood of being immunized with Penta-3 was higher for non-Pashtun ethnicity [adjusted odds ratio (aOR) 1.69; 95% CI 1.33-2.14], children of educated mothers, secondary or higher [aOR 2.95, 95% CI 2.34-3.71], and those whose fathers were formally employed (aOR 1.53; 95% CI 1.19-1.97). No association was seen by gender of child [aOR 0.89; 95% CI 0.73-1.08], and place of new born delivery [aOR 1.01; 95% CI 0.83-1.24]. Conclusion: Pockets of critically low under-vaccinations within the urban slums of Karachi are associated with Pashtun ethnicity, distance to the vaccination centre, lack of mothers' education and lack of stable family income as in the case of unemployed and daily wage-earning fathers. Recognition of these factors is required in designing contextually appropriate strategies to address vaccine inequity in urban settings.

COVID-19 vaccines: what happened to evidence-based medicine?

The UK government recently decided to extend the interval between the first dose of the Pfizer BioNTech and AstraZeneca COVID-19 vaccines from 3 weeks to 12 weeks to maximise the number of people receiving the initial dose, despite the trials only providing vaccine efficacy data based on a schedule of 21 days between doses. This editorial discusses whether there is evidence to support this policy change.

Axial Spondyloarthritis: Overcoming the Barriers to Early Diagnosis-an Early Inflammatory Back Pain Service.

PURPOSE OF REVIEW: To discuss the challenges to early diagnosis of axial spondyloarthritis (axSpA) and present the impact an early inflammatory back pain service (EIBPS) had on diagnostic delay in the UK. RECENT FINDINGS: Diagnostic delay in axSpA varies greatly worldwide, and has continued in the UK at an average of 8.5 years. Education, public awareness, and accessibility to inflammatory back pain (IBP) pathways are some of the key barriers to achieving a prompt diagnosis. A recent national inquiry has highlighted insufficiencies in the availability of specialist axSpA services and limited provision of education and training to first contact practitioners and allied healthcare providers. We demonstrate diagnostic delay in axSpA can be successfully reduced to 3 years when an early inflammatory back pain service is embedded within a rheumatology department alongside a local educational and awareness campaign. Sharing these experiences and outcomes will enable other departments to engage in best practice and achieve similar results, facilitating a timely and accurate diagnosis.

Therapies in ankylosing spondylitis-from clinical trials to clinical practice.

Until recently, the therapeutic options for patients suffering from active AS comprised NSAIDs and TNF inhibitor therapy. Although these are effective in a significant proportion of patients, not all patients respond and some are intolerant to these therapies. Therefore, there is a clear unmet treatment need in AS patients. This article reviews the evidence for targets currently being studied in AS. This includes the IL-12/23 inhibitor ustekinumab, the pan-Janus kinase inhibitor tofacitinib and the anti-IL-17A antibody secukinumab.